The objective of this application is to support the career development of Dr. Alicia Gerke. Dr. Gerke's long term career goal is to become a nationally recognized clinical investigator in identifying clinical and genetic risk factors for diagnosis and prognosis of rare diseases using novel internet-based research techniques. Dr. Gerke has assembled a team of experienced mentors (Drs. James Torner, Jeffrey Murray, Philip Polgreen, and Martha Monick) who bring expertise in complementary methodological areas and experience in nurturing young investigators. Using a recently developed national sarcoidosis registry, she will describe characteristics of the disease across the nation and identify clinical and genetic markers associated with outcomes. During the award, Dr. Gerke will become an expert in: 1) Patient-based investigation using internet-assisted (e-health) research, 2) Advanced clinical epidemiology methods for use in internet research, and 3) Identifying genetic markers of risk for disease prognosis and outcomes. These goals will be accomplished by coursework, readings, and research experiences guided by her mentors. Because clinical trials are difficult to perform in rare diseases such as sarcoidosis, much of clinical management is dictated by expert opinion. To date, the outcomes of varying diagnostic and treatment practices across the nation are largely unknown. Dr. Gerke will be using a sarcoidosis disease registry to aggregate data on a large national cohort of sarcoidosis patients in order to, first, understand the variability of diagnostic and treatment practices across the nation, and then, to identify clinical and genetic markers associated with progressive disease requiring long-term treatment. For Aim 1, Dr. Gerke will be expanding recruitment on an existing registry using internet and e-health based research approaches. Aim 2 will use registry data to define the pathways of diagnosis for sarcoidosis patients and establish risks associated with delays in diagnosis. Aim 3 will describe the treatment variability across the nation and identify treatment related practices associated with adverse outcomes. Aim 4 will be using DNA specimens from the registry biorepository to identify DNA methylation patterns that are associated with diagnosis and prognosis of patients with sarcoidosis. These projects are important to explore the characteristics of sarcoidosis patients on a national scale and identifying appropriate clinical an genetic markers of appropriate phenotypes for future clinical trials. Completion of these aims will provide the foundation for an independent research career for Dr. Gerke. Dr. Gerke's mentors and institution are committed to her success with resources and the environment in place to facilitate her career development.